Although morphological changes in collagen fibers of the periodontium are striking features of periodontal disease, data on the molecular alterations occurring in collagen during the pathogenesis of the disease are still lacking. Characterization of the collagenous tissue of the periodontium is necessary to provide valuable information on the role of intercellular macromolecules in periodontal disease. Detailed structural studies at the molecular level of human gingival collagen, from healthy and diseased tissues are proposed. Insoluble collagen will be solubilized by treatment with CNBr or by limited enzyme digestion. Physicochemical methods will be used for the characterization of gingival collagen at the molecular, subunit alpha- chain and CNBr-peptide levels. The acidic noncollagenous proteins, which we believe from preliminary work in our laboratory to be covalently bound to gingival matrix collagen, will also be studied. The molecular basis of connective tissue disorders in periodontal disease may be understood when these studies are correlated with histological and clinical observations. Thus, the state of collagen fibers in human gingiva may serve as a parameter to assess the progress of a pathologic condition.